Semin Thromb Hemost 2020; 46(07): 763-771
DOI: 10.1055/s-0040-1715456
Review Article

COVID-19 and Venous Thromboembolism: A Meta-analysis of Literature Studies

Alessandro Di Minno
1   Department of Pharmacy, Federico II University, Naples, Italy
Pasquale Ambrosino
2   Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
Ilenia Calcaterra
3   Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
Matteo Nicola Dario Di Minno
4   Department of Translational Medical Sciences, Federico II University, Naples, Italy
› Author Affiliations
Funding No financial support was received for this study.


Coronavirus disease 2019 (COVID-19) may have a wide spectrum of clinical presentations, leading in some cases to a critical condition with poor long-term outcomes and residual disability requiring post-acute rehabilitation. A major concern in severe COVID-19 is represented by a concomitant prothrombotic state. However, contrasting data are available about the prevalence of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and/or pulmonary embolism (PE). A detailed search on the association of COVID-19 with thromboembolic complications was conducted in the main electronic databases (PubMed, Web of Science, and Scopus) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The weighted mean prevalence (WMP) with 95% confidence interval (95% CI) was calculated with the random-effects model. Twenty studies enrolling 1,988 COVID-19 patients were included. The WMP of VTE was 31.3% (95% CI: 24.3–39.2%). The WMP of DVT was 19.8% (95% CI: 10.5–34.0%), whereas the WMP of PE was 18.9% (95% CI: 14.4–24.3%). Similar results were obtained when specifically analyzing studies on patients admitted to intensive care units and those on patients under antithrombotic prophylaxis. Regression models showed that an increasing age was associated with a higher prevalence of VTE (Z-score: 3.11, p = 0.001), DVT (Z-score: 2.33, p = 0.002), and PE (Z-score: 3.03, p = 0.002), while an increasing body mass index was associated with an increasing prevalence of PE (Z-score = 2.01, p = 0.04). Male sex did not impact the evaluated outcomes. The rate of thromboembolic complications in COVID-19 patients is definitely high. Considering the risk of fatal and disabling complications, adequate screening procedures and antithrombotic strategies should be implemented.

Publication History

Article published online:
03 September 2020

© 2020. Thieme. All rights reserved.

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  • References

  • 1 Zhu N, Zhang D, Wang W. et al; China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020; 382 (08) 727-733
  • 2 World Health Organization. Coronavirus disease 2019 (COVID-19). Situation Report, 1. 2020. Available at: . Accessed July 15, 2020
  • 3 World Health Organization. Coronavirus disease 2019 (COVID-19): Situation Report, 51. 2020 . Available at: . Accessed July 15, 2020
  • 4 Chan JF, Yuan S, Kok KH. et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 2020; 395 (10223): 514-523
  • 5 Guan WJ, Ni ZY, Hu Y. et al; China Medical Treatment Expert Group for COVID-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020; 382 (18) 1708-1720
  • 6 Chen N, Zhou M, Dong X. et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395 (10223): 507-513
  • 7 Wan S, Xiang Y, Fang W. et al. Clinical features and treatment of COVID-19 patients in northeast Chongqing. J Med Virol 2020; 92 (07) 797-806
  • 8 Wu P, Hao X, Lau EHY. et al. Real-time tentative assessment of the epidemiological characteristics of novel coronavirus infections in Wuhan, China, as at 22 January 2020. Euro Surveill 2020; 25 (03) 2000044
  • 9 Solomon MZ, Wynia MK, Gostin LO. Covid-19 crisis triage - optimizing health outcomes and disability rights. N Engl J Med 2020 ; Doi: 10.1056/NEJMp2008300 (epub ahead of print)
  • 10 Armitage R, Nellums LB. The COVID-19 response must be disability inclusive. Lancet Public Health 2020; 5 (05) e257
  • 11 Mo P, Xing Y, Xiao Y. et al. Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China. Clin Infect Dis 2020 ; Doi: 10.1093/cid/ciaa270 (epub ahead of print)
  • 12 Wu C, Chen X, Cai Y. et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020 ; Doi: 10.1001/jamainternmed.2020.0994 (epub ahead of print)
  • 13 Barbar S, Noventa F, Rossetto V. et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost 2010; 8 (11) 2450-2457
  • 14 Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339: b2535
  • 15 Goldhaber SZ, Morrison RB. Cardiology patient pages. Pulmonary embolism and deep vein thrombosis. Circulation 2002; 106 (12) 1436-1438
  • 16 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327 (7414): 557-560
  • 17 Sterne JA, Egger M, Smith GD. Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis. BMJ 2001; 323 (7304): 101-105
  • 18 Lodigiani C, Iapichino G, Carenzo L. et al; Humanitas COVID-19 Task Force. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res 2020; 191: 9-14
  • 19 Middeldorp S, Coppens M, van Haaps TF. et al. Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost 2020 ; Doi: 10.1111/jth.14888 (epub ahead of print)
  • 20 Bompard F, Monnier H, Saab I. et al. Pulmonary embolism in patients with Covid-19 pneumonia. Eur Respir J 2020 ; Doi: 10.1183/13993003.01365-2020 (epub ahead of print)
  • 21 Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost 2020; 18 (06) 1421-1424
  • 22 Demelo-Rodríguez P, Cervilla-Muñoz E, Ordieres-Ortega L. et al. Incidence of asymptomatic deep vein thrombosis in patients with COVID-19 pneumonia and elevated D-dimer levels. Thromb Res 2020; 192: 23-26
  • 23 Grillet F, Behr J, Calame P, Aubry S, Delabrousse E. Acute pulmonary embolism associated with COVID-19 pneumonia detected by pulmonary CT angiography. Radiology 2020 ; Doi: 10.1148/radiol.2020201544 (epub ahead of print)
  • 24 Helms J, Tacquard C, Severac F. et al; CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis). High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med 2020; 46 (06) 1089-1098
  • 25 Klok FA, Kruip MJHA, van der Meer NJM. et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 2020; 191: 145-147
  • 26 Lax SF, Skok K, Zechner P. et al. Pulmonary arterial thrombosis in COVID-19 with fatal outcome: results from a prospective, single-center, clinicopathologic case series. Ann Intern Med 2020 ; Doi: 10.7326/M20-2566 (epub ahead of print)
  • 27 Leonard-Lorant I, Delabranche X, Severac F. et al. Acute pulmonary embolism in COVID-19 patients on CT angiography and relationship to D-dimer levels. Radiology 2020 ; Doi: 10.1148/radiol.2020201561 (epub ahead of print)
  • 28 Llitjos JF, Leclerc M, Chochois C. et al. High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients. J Thromb Haemost 2020; 18 (07) 1743-1746
  • 29 Marone EM, Rinaldi LF. Upsurge of deep venous thrombosis in patients affected by COVID-19: preliminary data and possible explanations. J Vasc Surg Venous Lymphat Disord 2020; 8 (04) 694-695
  • 30 Poissy J, Goutay J, Caplan M. et al; Lille ICU Haemostasis COVID-19 Group. Pulmonary embolism in COVID-19 patients: awareness of an increased prevalence. Circulation 2020; 142 (02) 184-186
  • 31 Poyiadi N, Cormier P, Patel PY. et al. Acute pulmonary embolism and COVID-19. Radiology 2020 ; Doi: 10.1148/radiol.2020201955 (epub ahead of print)
  • 32 Ren B, Yan F, Deng Z. et al. Extremely high incidence of lower extremity deep venous thrombosis in 48 patients with severe COVID-19 in Wuhan. Circulation 2020; 142 (02) 181-183
  • 33 Spiezia L, Boscolo A, Poletto F. et al. COVID-19-related severe hypercoagulability in patients admitted to intensive care unit for acute respiratory failure. Thromb Haemost 2020; 120 (06) 998-1000
  • 34 Thomas W, Varley J, Johnston A. et al. Thrombotic complications of patients admitted to intensive care with COVID-19 at a teaching hospital in the United Kingdom. Thromb Res 2020; 191: 76-77
  • 35 Wichmann D, Sperhake JP, Lütgehetmann M. et al. Autopsy findings and venous thromboembolism in patients with COVID-19. Ann Intern Med 2020 ; Doi: 10.7326/M20-2003 (epub ahead of print)
  • 36 Wright FL, Vogler TO, Moore EE. et al. Fibrinolysis shutdown correlation with thromboembolic events in severe COVID-19 infection. J Am Coll Surg 2020; 231 (02) 193-203.e1
  • 37 Zhang L, Feng X, Zhang D. et al. Deep vein thrombosis in hospitalized patients with coronavirus disease 2019 (COVID-19) in Wuhan, China: prevalence, risk factors, and outcome. Circulation 2020; 142 (02) 114-128
  • 38 Clayton TC, Gaskin M, Meade TW. Recent respiratory infection and risk of venous thromboembolism: case-control study through a general practice database. Int J Epidemiol 2011; 40 (03) 819-827
  • 39 Malato A, Dentali F, Siragusa S. et al. The impact of deep vein thrombosis in critically ill patients: a meta-analysis of major clinical outcomes. Blood Transfus 2015; 13 (04) 559-568
  • 40 Thachil J, Srivastava A. SARS-2 coronavirus-associated hemostatic lung abnormality in COVID-19: Is it pulmonary thrombosis or pulmonary embolism?. Semin Thromb Hemost 2020 ; Doi: 10.1055/s-0040-1712155 (epub ahead of print)
  • 41 Ackermann M, Verleden SE, Kuehnel M. et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med 2020; 383 (02) 120-128
  • 42 Chernysh IN, Nagaswami C, Kosolapova S. et al. The distinctive structure and composition of arterial and venous thrombi and pulmonary emboli. Sci Rep 2020; 10 (01) 5112
  • 43 Chen G, Wu D, Guo W. et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest 2020; 130 (05) 2620-2629
  • 44 Huang C, Wang Y, Li X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395 (10223): 497-506
  • 45 Xiong M, Liang X, Wei YD. Changes in blood coagulation in patients with severe coronavirus disease 2019 (COVID-19): a meta-analysis. Br J Haematol 2020; 189 (06) 1050-1052
  • 46 Yang X, Yu Y, Xu J. et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med 2020; 8 (05) 475-481
  • 47 Zhou F, Yu T, Du R. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395 (10229): 1054-1062
  • 48 Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020; 18 (04) 844-847
  • 49 Taylor Jr FB, Toh CH, Hoots WK, Wada H, Levi M. Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 2001; 86 (05) 1327-1330
  • 50 Levi M, Thachil J, Iba T, Levy JH. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol 2020; 7 (06) e438-e440
  • 51 Babu AS, Vasanthan LT. Critical care rehabilitation - is it the answer for reducing morbidity in ARDS survivors? Regarding “Acute respiratory distress syndrome: a clinical review”. Pulm Circ 2012; 2 (02) 265
  • 52 Borg K, Stam H. Editorial: Covid-19 and physical and rehabilitation medicine. J Rehabil Med 2020; 52 (04) jrm00045
  • 53 Brugliera L, Spina A, Castellazzi P. et al. Rehabilitation of COVID-19 patients. J Rehabil Med 2020; 52 (04) jrm00046
  • 54 Godeau E, Debeaumont D, Artaud-Macari E, Lagache L, Bouar GL, Coquart J. Sequelae of acute respiratory distress syndrome: interest of rehabilitation. Case Rep Crit Care 2019; 2019: 7953141
  • 55 Herridge MS, Tansey CM, Matté A. et al; Canadian Critical Care Trials Group. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med 2011; 364 (14) 1293-1304
  • 56 Ambrosino P, Papa A, Maniscalco M, Di Minno MND. COVID-19 and functional disability: current insights and rehabilitation strategies. Postgrad Med J 2020 ; Doi: 10.1136/postgradmedj-2020-138227 (epub ahead of print)
  • 57 Simpson R, Robinson L. Rehabilitation after critical illness in people with COVID-19 Infection. Am J Phys Med Rehabil 2020; 99 (06) 470-474
  • 58 Favaloro EJ, Lippi G. Recommendations for minimal laboratory testing panels in patients with COVID-19: potential for prognostic monitoring. Semin Thromb Hemost 2020; 46: 379-382
  • 59 World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected. Interim guidance 28 January 2020. Available at: . Accessed July 15, 2020
  • 60 Thachil J, Tang N, Gando S. et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost 2020; 18 (05) 1023-1026
  • 61 Bikdeli B, Madhavan MV, Jimenez D. et al; Global COVID-19 Thrombosis Collaborative Group, Endorsed by the ISTH, NATF, ESVM, and the IUA, Supported by the ESC Working Group on Pulmonary Circulation and Right Ventricular Function. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. J Am Coll Cardiol 2020; 75 (23) 2950-2973
  • 62 Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood 2020; 135 (23) 2033-2040